Department of Medicine, Georgetown University School of Medicine, Washington, DC.
Division of Hematology and Oncology, Department of Medicine, MedStar Washington Hospital Center, Washington, DC.
Clin Lung Cancer. 2022 Jul;23(5):438-445. doi: 10.1016/j.cllc.2022.03.010. Epub 2022 Apr 29.
While the introduction of immune checkpoint inhibitors (ICI) such as pembrolizumab has significantly improved survival for patients with metastatic non-small cell lung cancer (NSCLC), there remains a need for improved predictive and prognostic biomarkers.
We conducted a retrospective, 3-center study using electronic medical record data for patients with stage IV NSCLC treated with first-line pembrolizumab, either as monotherapy or in combination with chemotherapy, between 2014 and 2019. We categorized variables as covariates or confounders. Covariates, which were the focus of analysis due to their emerging prognostic value, included pretreatment body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), albumin, and antibiotic exposure. Confounders, which highlighted characteristics for each patient and their cancer, included sex, age at start of immunotherapy, Programmed death-ligand 1 (PD-L1) expression, performance status (PS), tumor mutational burden and whether pembrolizumab was given as monotherapy or in combination with chemotherapy. The association between these variables with time to treatment failure (TTF) and overall survival (OS) was assessed using Kaplan-Meier method and Cox proportional hazards models.
One hundred thirty-six patients were included in our study. Antibiotics usage, serum albumin, and NLR have univariate relationships with TTF. Serum albumin, NLR, and BMI were associated with OS in univariate analyses. In our multivariate analysis, antibiotic usage had a strong negative association with TTF when adjusting for all 6 confounders.
Pretreatment usage of antibiotics, as well as albumin, NLR, and BMI have potential to predict treatment outcomes in patients with advanced NSCLC receiving first-line immunotherapy.
虽然免疫检查点抑制剂（ICI）的引入，如 pembrolizumab，显著改善了转移性非小细胞肺癌（NSCLC）患者的生存，但仍需要改善预测和预后生物标志物。
我们进行了一项回顾性的、3 中心的研究，使用电子病历数据，对 2014 年至 2019 年间接受一线 pembrolizumab 治疗的 IV 期 NSCLC 患者进行研究，这些患者接受 pembrolizumab 单药治疗或联合化疗。我们将变量分类为协变量或混杂因素。由于其具有预测价值，协变量（分析的重点）包括预处理的体重指数（BMI）、中性粒细胞与淋巴细胞比值（NLR）、白蛋白和抗生素暴露。混杂因素突出了每位患者及其癌症的特点，包括性别、免疫治疗开始时的年龄、程序性死亡配体 1（PD-L1）表达、表现状态（PS）、肿瘤突变负担以及 pembrolizumab 是单药治疗还是联合化疗。使用 Kaplan-Meier 方法和 Cox 比例风险模型评估这些变量与治疗失败时间（TTF）和总生存（OS）之间的关联。
我们的研究纳入了 136 名患者。抗生素使用、血清白蛋白和 NLR 与 TTF 具有单变量关系。血清白蛋白、NLR 和 BMI 在单变量分析中与 OS 相关。在我们的多变量分析中，在调整了所有 6 个混杂因素后，抗生素使用与 TTF 具有很强的负相关。
在接受一线免疫治疗的晚期 NSCLC 患者中，抗生素的预处理使用以及白蛋白、NLR 和 BMI 具有预测治疗结果的潜力。
